Y-6868300-C-T

Variant names:

• chrY-6868300-C-T
• NM_001143.2:c.310G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001143.2(AMELY):​c.310G>A​(p.Val104Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 0)
• Consequence: AMELY NM_001143.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0390

Genes affected

AMELY (HGNC:462): (amelogenin Y-linked) This gene encodes a member of the amelogenin family of extracellular matrix proteins. Amelogenins are involved in biomineralization during tooth enamel development. Mutations in a related gene on chromosome X cause X-linked amelogenesis imperfecta. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.21461642).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMELY	NM_001143.2	c.310G>A	p.Val104Ile	missense_variant	Exon 6 of 7	ENST00000651267.2	NP_001134.1
AMELY	NM_001364814.1	c.352G>A	p.Val118Ile	missense_variant	Exon 6 of 7		NP_001351743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMELY	ENST00000651267.2	c.310G>A	p.Val104Ile	missense_variant	Exon 6 of 7		NM_001143.2	ENSP00000498344.1
AMELY	ENST00000383036.1	c.352G>A	p.Val118Ile	missense_variant	Exon 5 of 6	5		ENSP00000372505.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.30	.;T
FATHMM_MKL	Benign	0.33	N
LIST_S2	Uncertain	0.86	D;D
M_CAP	Benign	0.063	D
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-0.48	T
MutationAssessor	Benign	1.0	.;L
PROVEAN	Benign	-0.26	N;N
REVEL	Benign	0.25
Sift	Benign	0.13	T;T
Sift4G	Benign	0.32	T;T
Polyphen		0.33	B;P
Vest4		0.14
MutPred		0.56		.;Loss of catalytic residue at V118 (P = 0.1458);
MVP		0.77
MPC		0.0017
ClinPred		0.23	T
GERP RS		-1.0
Varity_R		0.25
gMVP		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrY-6736341;